1e1x
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HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR NU6027
OverviewOverview
Substituted guanines and pyrimidines were tested as inhibitors of cyclin, B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2., O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1, and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12, +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu, 81, N-3 to Leu 83, and 2-NH2 to Leu 83). The triplet of hydrogen bonding, and CDK inhibition was reproduced by, 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values:, CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Against human tumor, cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values, of 13 +/- 7 microM and 10 +/- 6 microM, respectively), with a pattern of, sensitivity distinct from flavopiridol and olomoucine. These CDK, inhibition and chemosensitivity data indicate that the distinct mode of, binding of NU2058 and NU6027 has direct consequences for enzyme and cell, growth inhibition.
About this StructureAbout this Structure
1E1X is a Single protein structure of sequence from Homo sapiens with ACE and NW1 as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
ReferenceReference
Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles., Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Garman EF, Gibson AE, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Lawrie AM, Newell DR, Noble ME, Sausville EA, Schultz R, Yu W, J Med Chem. 2000 Jul 27;43(15):2797-804. PMID:10956187
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